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October 15, 2012

Phase Separation Could Have Played Role In Early RNA Compartmentalization

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redOrbit Staff & Wire Reports - Your Universe Online

A chemical model developed by a team of US researchers shows how the Earth's first life forms may have packaged the genetic coding material known as ribonucleic acid (RNA), demonstrating one of the earliest steps that could have paved the way for the formation of cellular life some four billion years ago.

The Penn State University scientists behind the project used a type of macromolecule called polymers to create primitive cell-like structures. They then infused those structures with RNA and successfully demonstrated how those molecules would chemically react during simulated early-Earth conditions. Their findings were published online by the journal Nature Chemistry on Sunday.

"In modern biology, all life, with the exception of some viruses, uses DNA as its genetic storage mechanism," the university explained in an October 14 press statement. "According to the 'RNA-world' hypothesis, RNA appeared on Earth first, serving as both the genetic-storage material and the functional molecules for catalyzing chemical reactions, then DNA and proteins evolved much later."

RNA can take on several different molecular conformations while DNA cannot, which means that the former (but not the latter) is "functionally interactive on the molecular level," they said. One missing piece of the RNA-world hypothesis, however, is "compartmentalization," according to Penn State Chemistry Professor and study co-author Philip Bevilacqua. To support the RNA-world belief, the molecules that comprise the genetic material must not only be present, but must also be able to hold together in a small area.

In order to test how early cell-like structures could have formed and packaged RNA molecules, graduate students Christopher Strulson and Rosalynn Molden created non-living model cells using solutions of the polymers polyethylene glycol (PEG) and dextran, the university explained. They discovered that the molecules were able to physically associate and complete chemical reactions once RNA was inserted into dextran-rich compartments.

"Interestingly, the more densely the RNA was packed, the more quickly the reactions occurred," said Bevilacqua. "We noted an increase in the rate of chemical reactions of up to about 70-fold. Most importantly, we showed that for RNA to 'do something' -- to react chemically -- it has to be compartmentalized tightly into something like a cell. Our experiments with aqueous two-phase systems (ATPS) have shown that some compartmentalization mechanism may have provided catalysis in an early-Earth environment."

While the researchers say they are not suggesting that PEG and dextran were the actual polymers that were present during the planet's earliest days, they do believe that their study demonstrates that phase separation -- a process which high-concentrations of polymers in a solution lead to separation (much like oil and water) -- could be "a plausible route to compartmentalization." They also say that they found that the longer that a string of RNA was, the more densely it would be compacted into the dextran compartments.

"We hypothesize that this research result might indicate some kind of primitive sorting method," Bevilacqua explained. "As RNA gets shorter, it tends to have less enzyme activity. So, in an early-Earth system similar to our dextran-PEG model system, the full-length, functional RNA would have been sorted and concentrated into one phase, while the shorter RNA that is not only less functional, but also threatens to inhibit important chemical reactions, would not have been included."

They added that they hope to test their hypothesis using other types of polymers in future studies.

Image 2 (below): Shown are RNA strands (blue) and RNA enzymes (red) coming together within droplets of dextran. Scientists at Penn State have shown that this compartmentalization helps to catalyze chemical reactions. Credit: C. A. Strulson